Abstract

Background

Inhalative nanocarriers for local or systemic therapy are promising. Gold nanoparticles
(AuNP) have been widely considered as candidate material. Knowledge about their interaction
with the lungs is required, foremost their uptake by surface macrophages and epithelial
cells.

Diseased lungs are of specific interest, since these are the main recipients of inhalation
therapy. We, therefore, used Scnn1b-transgenic (Tg) mice as a model of chronic obstructive
pulmonary disease (COPD) and compared uptake and localization of inhaled AuNP in surface
macrophages and lung tissue to wild-type (Wt) mice.

Results

AuNP were mainly found as singlets or small agglomerates of ≤ 100 nm diameter, at
the epithelial surface and within lung-surface structures. Macrophages contained also
large AuNP agglomerates (> 100 nm). At 0 h after aerosol inhalation, 69.2±4.9% AuNP
were luminal, i.e. attached to the epithelial surface and 24.0±5.9% in macrophages
in Scnn1b-Tg mice. In Wt mice, 35.3±32.2% AuNP were on the epithelium and 58.3±41.4%
in macrophages. The percentage of luminal AuNP decreased from 0 h to 24 h in both
groups. At 24 h, 15.5±4.8% AuNP were luminal, 21.4±14.2% within epithelial cells and
63.0±18.9% in macrophages in Scnn1b-Tg mice. In Wt mice, 9.5±5.0% AuNP were luminal,
2.2±1.6% within epithelial cells and 82.8±0.2% in macrophages. BAL-macrophage analysis
revealed enhanced AuNP uptake in Wt animals at 0 h and in Scnn1b-Tg mice at 24 h,
confirming less efficient macrophage uptake and delayed clearance of AuNP in Scnn1b-Tg
mice.